Day 3: General Anaesthetic Agents: Intravenous Flashcards
What role do induction agents play in anesthesia?
Induction agents initiate anesthesia by producing loss of consciousness.
How quickly do true IV induction agents produce loss of consciousness?
True IV induction agents typically produce loss of consciousness within one arm-brain circulation time, approximately 30 seconds.
What is the approximate duration of action for a single dose of an induction agent?
A single dose of an induction agent wears off after a few minutes
Why is maintenance anesthesia necessary after induction?
Maintenance anesthesia is required to sustain the anesthetic state throughout the procedure.
What is the significance of the arm-brain circulation time in relation to induction agents?
Arm-brain circulation time is significant as it represents the time it takes for a drug administered intravenously to reach the brain and induce anesthesia.
classification of agents
-rapidly acting “true induction agents”
- slower acting
rapidly acting
Thiopentone
Etomidate
Propofol
Ketamine
slower acting
Benzodiazepines (midazolam)
Neuroleptic-anaesthetics
Opioids (in large doses)
advantages of IV induction
-Rapid onset of action
-More pleasant & acceptable for the patient
-Pollution free
-Low incidence of side-effects
-Smooth induction with rapid transfer through the classic stages of anaesthesia
disadvantages of IV induction
-Requires intravenous access
-It is easy to give too much …. side-effects
-No removal of drug via the lungs as with inhalational
-Recovery requires
*Redistribution
*Metabolism
*Excretion
-Sudden loss of normal protective reflexes
mechanism of action
-Most sedative hypnotics exert their effect via the inhibitory GABAA receptors
*GABA – γ (gamma)-aminobutyric acid
*Increased chloride conductance → hyperpolarisation → neuronal inhibition
-Some inhibit the release of glutamate, an excitatory amino acid, in brain
what is pharmacokinetics
Pharmacokinetics refers to the processes by which a drug is:
-Taken up by the body (absorption)
-Distributed to various tissues (distribution)
-Metabolised (usually via the liver)
-Excreted (e.g kidneys, GIT)
pharmacodynamics
Pharmacodynamics refers to the drug’s effects on the body
What factors influence the onset of action of intravenous anesthetics?
The onset of action of intravenous anesthetics depends on factors such as
-speed of injection,
-lipid solubility,
-protein binding, and
-blood flow to the brain.
What is the significance of the arm-brain circulation time in pharmacokinetics?
Arm-brain circulation time is crucial as it represents the time it takes for the drug to reach the effect site (the brain) by crossing the Blood-Brain Barrier.
How does recovery from intravenous anesthesia occur?
Recovery from intravenous anesthesia involves redistribution from vessel-rich to vessel-poor organs, metabolism, and excretion.
What processes contribute to the redistribution of intravenous anesthetics from vessel-rich to vessel-poor organs?
Intravenous anesthetics redistribute from the brain to other tissues, such as muscles, as anesthesia wanes.
How are intravenous anesthetics metabolized and excreted from the body during recovery?
Metabolism and excretion processes remove intravenous anesthetics from the body, contributing to recovery.
What is redistribution in the context of intravenous anesthesia?
Redistribution refers to the movement of intravenous anesthetic drugs from the brain to other less well-perfused tissues in the body.
How does redistribution contribute to the patient waking up after IV induction?
After IV induction, the patient wakes up due to redistribution, as the drug moves away from the brain.
Why does rapid awakening occur after redistribution?
Rapid awakening occurs because low concentrations of the drug remain in the brain, impairing concentration and higher functioning.
rapid awakening is not because of metabolism or excretion
What effect does the low concentration of the drug remaining in the brain have on the patient?
The low concentration of the drug in the brain post-redistribution can impair cognitive functions.
What precautions are recommended regarding driving and decision-making post-anaesthesia?
Patients are advised not to drive or make important decisions for 48-72 hours post-anaesthesia due to these effects.
the ideal IV induction agent
-smooth and rapid onset of action
-inexpensive
-rapid recovery
-minimal side effects/ toxicity
-no pain on injection
practical points with IV induction
Reduce pain on injection
-IV lignocaine 10-20mg in syringe when giving propofol
-New, large-bore, free-running IV line
Titrate to effect….. You can always give more
Less in elderly …. More in children
ketamine
unique: dissociative anaesthetic and analgesic
The international colour coding for all true IV induction agents is
yellow
The international colour coding for IV sedatives is
orange
What is the chemical composition of propofol?
Propofol’s chemical name is 2,6 di-isopropylphenol.
How is propofol prepared for administration due to its lack of solubility in water?
Propofol is prepared as an emulsion due to its insolubility in water.
What components are used to prepare propofol as an emulsion?
The components used to prepare propofol as an emulsion include soya bean oil, egg phosphatide (egg yolk), and glycerol.
What are the concerns regarding the use of fat emulsion in propofol?
Concerns regarding the use of fat emulsion in propofol include its potential as a culture medium for microorganisms.
What are the recommended guidelines for the use of propofol regarding its shelf life and administration?
Propofol should be used within 6 hours of opening.
What are the available sizes and concentrations of propofol ampoules?
Multiple ampoule sizes are available, including 20ml, 50ml, or 100ml, with concentrations of 1% or 2% (1% equals 10mg/ml).
What is the lipid solubility of propofol?
Propofol is extremely lipid-soluble.
How does propofol interact with the blood-brain barrier?
Propofol easily crosses the blood-brain barrier.
What type of metabolism does propofol undergo, and how does it contribute to rapid plasma clearance?
Propofol undergoes extra-hepatic metabolism, leading to rapid plasma clearance and emergence.
What are the versatile uses of propofol in anesthesia?
Propofol is versatile and can be used for
-induction,
-maintenance (Total Intravenous Anaesthetic - TIVA), and
-sedation in lower doses.
propofol: induction doses
Adults: 2 – 2.5 mg/kg
Elderly: 1 – 1.5 mg/kg
Children: 2.5 – 3 mg/kg
propofol: organ effects
CNS
CVS
Respiratory
GIT
Metabolic
propofol: CNS effects
Rapid LOC + recovery
Less hangover effect than other induction agents or gases
No real excitatory effects
Very slight analgesic effect
propofol: CVS effects
-Dose-dependent cardiovascular depression
-↓ Systemic Vascular Resistance (SVR)
-↓ BP
-Slight ↑ HR
-Large doses administered rapidly significantly depress the CVS vs. small doses administered slowly
-Careful in elderly and fluid-depleted patients
- Not suitable in shock / haemorrhage / significant CVS compromise
Propofol: Respiratory effects
-Dose-dependent depression
-Apnoea on induction close to 100%
-Inhibits laryngeal reflexes
-No histamine release
Propofol: other effects
-Anti-emetic useful in patients with PONV
-Propofol Infusion Syndrome (PRIS)
*Seen with prolonged high-dose infusions
*Presents with lipaemia, metabolic acidosis, myopathy
*May be fatal
Propofol: Ideal for these specific scenarios
TIVA
Conscious sedation
Asthma
Porphyria
History of PONV
History of Malignant Hyperthermia
What is a major concern associated with propofol administration?
Cardiovascular depression is a major concern with propofol.
In which patient populations should caution be exercised when administering propofol?
Elderly
Cardiac failure
Hypovolaemia
Fixed cardiac output
–Aortic / Mitral stenosis
–HOCM
What is the most common use of propofol in anesthesia?
Propofol is most commonly used as an intravenous induction agent in anesthesia.
What physical form does thiopentone typically have?
Thiopentone typically exists as a yellow powder.
How is thiopentone typically prepared for use?
Thiopentone is usually mixed with water or normal saline for administration.
What is the pH of thiopentone solution?
The pH of thiopentone solution is 10.5.
How long is thiopentone solution stable for?
Thiopentone solution is stable for 24-48 hours.
induction dose of thiopentone
Adults: 3 – 5mg/kg
Children: 5-6mg/kg
Caution in elderly
thiopentone: CNS effects
-LOC in 30 sec
*Classically described for Rapid Sequence Induction
-Smooth, no reflex movements or coughing
-Antanalgesic may LOWER pain threshold
-Anti-convulsant
-Used in treatment of STATUS EPILEPTICUS
-Neuroprotective
*↓CMRO2
*↓ ICP
Thiopentone: CVS effects
↓ Cardiac output (10–20%)
-Vasodilatation
-Negative inotropy
-↓ central catecholamine release
Compensatory ↑HR
Exaggerated response with
-Elderly
-Cardiac failure
-Fixed cardiac output
-Hypovolaemia
Thiopentone: Respiratory effects
-Dose-dependent apnoea
0No depression of laryngeal reflexes
-Histamine release: careful in asthmatics
thiopentone: other effects
-Irritant to tissues
*Venous thrombosis with older 5% solutions
-Intra-arterial injection is a disaster
*Precipitation of solid crystals of thiopentone in arteries due to blood pH of 7.4
*Acute ischaemia of limb
-No specific concerns with regards to renal, hepatic or GIT side-effects
Thiopentone: Contraindications
Absolute:
-Porphyria
-Known allergy (rare)
Relative:
-Asthma
-Cardiovascular instability
What are the typical physical properties of etomidate?
Etomidate typically exists as a clear solution with propylene glycol.
In what form is etomidate commonly available (ampoule size and concentration)?
It is commonly available in 10 ml ampoules with a concentration of 2 mg/ml, resulting in 20 mg in each ampoule
Describe the appearance of etomidate solutions.
Etomidate solutions can appear as either a clear solution or an opaque white emulsion, similar to propofol.
What is a notable characteristic of etomidate solutions upon injection?
Both forms of etomidate solutions are known to cause pain upon injection.
etomidate dose
0.2–03 mg/kg (Adult: typically 16-20 mg)
What is the typical duration of recovery after administering etomidate?
Etomidate typically leads to rapid recovery within 6-8 minutes after administration.
Is the effect of repeated doses cumulative?
Repeated doses of etomidate do not result in cumulative effects.
Why is etomidate not suitable for infusion?
Etomidate is not suitable for infusion due to its potential for causing adrenocortical suppression.
For what purpose is etomidate primarily used?
Etomidate is primarily used for induction of anesthesia and is not intended for continuous infusion.
etomidate: CNS
-Rapid LOC
-Myoclonus and involuntary movements
*Reduced by concurrent opiate and benzodiazepine use
etomidate: CVS
Most stable
Little change in BP or HR
etomidate: respiratory
Minimal respiratory depression
No histamine release
Least likely to cause anaphylaxis
etomidate: GIT
Severe PONV!
“VOMIDATE”
etomidate: endocrine
Inhibition of steroid synthesis (cortisol & aldosterone)
What are the typical concentrations of ketamine available in solutions?
Ketamine is available in solutions of 1% (10mg/ml) and 10% (100mg/ml).
Is ketamine typically stored in single-use vials or multi-use vials?
Ketamine is commonly stored in multi-use vials.
What type of receptor does ketamine antagonize?
Ketamine antagonizes the NMDA receptor.
Does ketamine cause pain upon injection?
Ketamine typically does not cause pain upon injection.
Besides inducing loss of consciousness, what other effect does ketamine have?
Ketamine acts as a potent analgesic in addition to inducing loss of consciousness.
In what routes can ketamine be administered?
Ketamine can be administered intravenously (IV), intramuscularly (IM), and even orally.
ketamine: CNS effects
-Phencyclidine derivative
-Dissociative anaesthetic
-Complete analgesia
-↑ ICP and IOP
-Psychiatric reactions:
*Hallucinations and emergence delirium
*Less in children, males, elderly and repeated administration
*Worse if patient stimulated on awakening
ketamine: CVS effects
-CENTRAL sympathetic stimulant
↑ HR
↑ BP
↑ C.O.
↑ SVR
-But… direct myocardial depressant
-Not arrhythmogenic
ketamine: respiratory effects
-Minimal or no respiratory depression
-Preserved pharyngeal reflexes
-Maintains airway
*Do not necessarily need to intubate or insert LMA
-Bronchodilator
*Sympathetic stimulation
*Safe in asthma (no histamine release
*Last line treatment of status asthmaticus
-Increased salivation and bronchial secretions
*Use anti-sialogogue (anticholinergic like atropine or glycopyrrolate
ketamine: other considerations
Causes postoperative nausea and vomiting (PONV)
May cause uterine contractions (1st trimester)
A drug of abuse (“Special K”, “Vitamin K”) due to its hallucinogenic effects
ketamine indications
-Sick and unstable adults and children
-Burns surgery
-Debridement
-Change of dressings
-Short diagnostic procedures
-Analgesia
-Battlefield anaesthesia
-Status asthmaticus
ketamine contraindications
-CVS pathology
*IHD, hypertension, AAA, CCF
-↑ ICP
-↑ IOP and “open eye”
-Psychiatric patients
-Epileptics
-Thyrotoxicosis
-Early pregnancy
What receptors do benzodiazepines act on?
Benzodiazepines act on the GABA receptors.
What is the main use of benzodiazepines in anaesthesia?
They are mainly used as sedatives for premedication and intra-operative sedation in anaesthesia.
rarely used as induction agents
benzodiazepines: oral medication
Lorazepam, temazepam, diazepam, midazolam
benzodiazepines
Midazolam
What are the available preparations of midazolam?
Midazolam is available in 5 mg ampoules (1 mg/ml) and 15 mg ampoules (5 mg/ml).
What are the concentrations of midazolam in the 5 mg and 15 mg ampoules?
The concentration of midazolam is 1 mg/ml in 5 mg ampoules and 5 mg/ml in 15 mg ampoules.
What caution should be taken when checking midazolam ampoules?
Care should be taken when checking midazolam ampoules as the 5 mg and 15 mg ampoules may look identical.
midazolam: pharmacokinetics
shorter duration of action
midazolam dose
Premed: 0.5mg/kg
Adults 7.5-15mg orally
Works within 30 min
Kids – 0.25-0.5mg/kg PO
Induction: 0.1-0.3mg/kg
Sedation: 0.1mg/kg
Less with elderly
midazolam: CNS
-Induction does not occur within 1 arm-brain circulation time
*Takes 55 - 140sec
-Anterograde amnesia
-Anxiolysis
-Sedation
-Prolonged recovery
midazolam CVS
Stable
Often used in cardiac surgery
midazolam Respiratory
Little effect
midazolam GIT
Low incidence PONV
midazolam UTERUS
Crosses placenta and cause floppy neonate
Flumazenil
Specific benzodiazepine antagonist
flumazenil
Dose: 0.2mg IV short acting
Total Intravenous Anaesthesia (TIVA)
Ideal: PROPOFOL
Ketamine
TIVA: indications
-Risk of malignant hyperthermia
-Severe PONV in prior case
-Day-case surgery
-Cheaper than gases
TIVA benefits
Rapid wake-up
No PONV
TIVA requirements
infusion pumps
